Numerous studies have reported neurocognitive impairments associated with chronic marijuana use. Given that the hippocampus contains a high density of cannabinoid receptors, hippocampal-mediated cognitive functions, including visuospatial memory, may have increased vulnerability to chronic marijuana use. Thus, the current study examined brain activation during the performance of a virtual analogue of the classic Morris water maze task in 10 chronic marijuana (MJ) users compared to 18 nonusing (NU) comparison subjects. Imaging data were acquired using blood oxygen level-dependent (BOLD) functional MRI at 3.0？Tesla during retrieval (hidden platform) and motor control (visible platform) conditions. While task performance on learning trials was similar between groups, MJ users demonstrated a deficit in memory retrieval. For BOLD fMRI data, NU subjects exhibited greater activation in the right parahippocampal gyrus and cingulate gyrus compared to the MJ group for the Retrieval-Motor Control contrast (NU > MJ). These findings suggest that hypoactivation in MJ users may be due to differences in the efficient utilization of neuronal resources during the retrieval of memory. Given the paucity of data on visuospatial memory function in MJ users, these findings may help elucidate the neurobiological effects of marijuana on brain activation during memory retrieval. 1. Introduction Research on marijuana (MJ) use continues to be a major area of investigation, since MJ remains the most widely used illicit drug in several countries, including the United States [1]. Daily, long-term, and frequent MJ use can have serious adverse effects on mental and physical health and can affect work performance, family, and school functioning [2]. In 2009, epidemiological data (Treatment Episode Data Set) indicated that MJ was associated with 740,800 substance abuse treatment admissions, with daily use being reported in 23% of treatment entries [2]. Nearly half (46.3%) of daily MJ admissions occurred in individuals between ages 26 and 40 years old and 34.2% between ages 18 and 25 years old [2]. In addition, there has been a rise in the prevalence of MJ use among youth, with 36.4% and 22.6% of high school seniors reporting past year and past 30 days use, respectively. Given that rapid brain maturation occurs from adolescence into the early twenties [3, 4], a time when MJ use is often initiated and tends to increase, identifying neurobiological vulnerabilities associated with MJ use is critical. Short-term effects of MJ have been reported across a number cognitive domains (for review
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